Bomback Andrew S, Tumlin James A, Baranski Joel, Bourdeau James E, Besarab Anatole, Appel Alice S, Radhakrishnan Jai, Appel Gerald B
Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Drug Des Devel Ther. 2011 Mar 14;5:147-53. doi: 10.2147/DDDT.S17521.
A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.
Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.
Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.
ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.
一种合成促肾上腺皮质激素（ACTH）类似物在欧洲已显示出对肾病综合征的原发性和继发性治疗效果，但在美国尚无使用天然、高度纯化的ACTH凝胶制剂治疗肾病综合征的公开经验。因此，我们在美国研究了ACTH凝胶用于肾病综合征的情况。
21例肾病综合征患者在美国非研究环境下接受ACTH凝胶治疗，治疗起始时间为2009年12月31日之前，随访时间至少6个月。我们将完全缓解定义为肾功能稳定且蛋白尿降至<500mg/天，部分缓解定义为肾功能稳定且蛋白尿从500至3500mg/天减少>50%。
21例肾病综合征患者接受了治疗：11例为特发性膜性肾病（iMN），4例为膜增生性肾小球肾炎（MPGN），1例为局灶节段性肾小球硬化（FSGS），1例为微小病变病（MCD），1例为免疫球蛋白A（IgA）肾病，1例为Ⅴ类系统性红斑狼疮（SLE）肾小球肾炎，1例为单克隆弥漫性增生性肾小球肾炎，1例为未行肾活检的肾病综合征。3例患者将ACTH用作初始治疗；其余患者此前平均已失败2.3种免疫抑制方案。11例患者实现了完全或部分缓解，4例（19%）完全缓解。在实现缓解的11例患者中，9例为iMN，1例为FSGS，1例为IgA肾病。在11例iMN患者中，尽管此前平均已失败2.4种治疗，但仍有3例（27%）完全缓解，6例（55%）部分缓解。5例患者报告有类类固醇不良反应，但无严重感染。局限性在于短期随访的回顾性数据分析。
ACTH凝胶可能是治疗膜性肾病所致难治性肾病综合征的一种可行选择。短期数据表明缓解率可能接近80%。
